OBJECTIVES: 1) To obtain highly purified populations of cells from normal mouse spleen and peritoneal exudite which restore bone resorption when given to sublethally irradiated, syngenic osteopetrotic mice. 2) By application of specific immunologic, CFU-s bioassay and cell tracer procedures to identify the cell type(s) responsible for restoration of bone resorption in mice with congenital osteopetrosis. Normal mouse peritoneal exudate cells were assayed for bone resorption restorative activity (BRRA) after eliminating all cell types except monocytes and macrophages. Irradiation at 900 r was used to eliminate all cells capable of mitotic activity. Anti-0 and anti-mu immunoglobulins were used to eliminate T- and B-lymphocytes. As a control, non-adherent peritoneal cells were tested for BRRA. Normal mouse spleen has been fractionated by velocity sedimentation at unit gravity (G-1 sed.) in a sucrose gradient. Small (less than 8 microns diam.) (intermediate 8-13 microns diam.) and large (less than 13 microns diam.) were bioassayed for BRRA and characterized by the same procedures used in analyses of peritoneal exudate cells. Various cell markers will be used in an effort to a) identify the osteoclast precursor, b) determine the life span and time required to generate new osteoclasts.